A.bac: Protein Synthesis Inhibitors Flashcards
50S Antibacterial agents
50S➡️Macrolides: Erythromycin, Azithromycin, Clarithromycin
Chloramphenicol, Lincosamides, Clinda
30S➡️ AG: Genta, Strepto, Kana
Tetra: T, Doxy, Mino
Bacteriostatic antibacterials:
TEST CC: Tetra, Eryth, Sulfa drugs, Trimetho, Clinda, Chloram
Macrolides chemical struc. and CI
Large lactones ring of 12 or 14 or 16 atoms are att. to amino sugar (hexose) & neutral sugar by glycosidic link.
CI hepatic failure.
These macrolides produce KETAL metabolite resp for GI irritation.
CYP3A4 inhibitors for macrolides
Eryth and Clarith, also potent CYP3A4 inhibitors whereas Azith is weak.
Eryth chem. struc, common SE and stability
Lactone ring + desoamine (amino sugar) + cladinose (neutral sugar).
Unstable to acids, bases & high temperature.
Azith stability and phkinetics
Stable to acids, bases & high temp, thus less gastric upset.
Long half life, greater and longer tissue penetration and covers H. influenza.
Clarith phkinetics
The enhanced lipophilic allows for lower or less frequent doses
What drugs potentiate this Digoxin toxicity
Macrolides: Eryth and Clarith, Tetracyclines
*and Macrolides may potentiate Theophylline levels also.
With Clinda this is taken with caution and require monitoring in patient receiving what drug tx?
Warfarin— INR
drug of choice in traveler diarrhea for person traveling to Thailand.
Prophylaxis?
Azith
Doxy- prophy
Erythromycin is effective against?
Erythromycin estolate side effects?
Macrolides storages
gram +ve cocci
SEs reversible cholestatic hepatitis, jaundice, and
fever
Eryth -ref, A and C room temp
Tet. t1/2 is shortened by CYP450 induction of what drugs and bev.?
Carbamazepine
Phenytoin
Barbiturates
Chronic alcohol intake
Tet can stain teeth and discoloration leading to?
Deformity and growth intake, teeth fluorescence, discoloration and enamel dysplasia
Tet chemical instability and structure.
Tetracycline a-stereo orientation of the C4 dimethylamino-moiety is essential for the bioactivity.
Epitetracycline is inactive drug.
Tet MOA
Enter cells by passive diffusion or by (in part) active transport. Once inside the cell, tet bind REVERSIBLY TO 30s subunit of bacterial ribosome, blocking binding of aminoacyl-tRNA to receptor site on mRNA was ribosome complex. This prevents additional a.a. to growing peptide
Tet absorption occurs where and is impaired by what food/factors?
Upper small intestine
By: Food (exc, Doxy and Mino), Ions (Ca, Mg, Fe, Al), Dairy prod. and antacids, alkaline pH
Photo toxicity of which Tetracycline
Demecycline: Tetracycline with C7 chlorine, absorb light in the visible region leading to free radical generation and potentially cause severe erythema to sensitive patient on exposure to sunlight.
Doxy and Mino
Doxy: Less SEs. Renally safe. More photosensitive
Mino: High SEs. Has reactive a.a. causes serum sickness (discoloration of nails, bones, teeth) More eff. for acne due to lip. sol. OD= 90-100% bioav.
BOTH in doses >100mg ➡️Vestibular toxicity (vertigo, ataxia, n) dizzy HE
Expired tetracycline causes what syndrome?
And GI adverse effects?
Funconi like syndrome (renal tubular necrosis, diabetes like symptoms) and extreme cases has been fatal.
GI: Tet modify intestinal flora➡️ suppression of coliform bacteria an overgrowth of pseudomonas, proteus, Staph, Clostridia and Candida
DOC for diarr prophylaxis. W/wo food?
Doxy.
WITH or AFTER food, BUT EMPTY STOMACH BETTER ABSORPTION
Optical isomerism of Tet.
Epimerization➡️ Epitetracycline
Mycoplasma pneumonia is treated by?
Macrolides and Tetracyclines
Most common complication of clindamycin is?
Symptoms include? Tx by?
P.colitis (diarrhea): fever, abdominal pain, and bloody
stools.
Oral vancomycin or metronidazole, OTC antidiarrheals not effective
Clindamycin active against?
Usual dose?
Gram +ve, -ve and anaerobic bacteria.
150-300mg q8h adults
10-20mg/kg/day q8h children
Clindamycin can cause what blood complications?
Blood dyscariasis (esonophilia, thrombocytopenia, leukopenia)
Clindamycin suspension stored at?
should be taken?
available dosage forms?
Room temperature
With or without food
IV, oral and suspension
Derivation of Clindamycin
Chlorine-substituted derivative of Lincomycin, derived from Streptomyces lincolnensis
-50S -Bacteriostatic -Bioav: PO»IV
Chloramphenicol
usual dose: 50-100mg/kg/day
oral: Chloramphenicol palmitate *PO
IV: Chloram succinate *suk-suk
Chloramphenicol metabolism and ADE
Metabolized in the liver by GLUCURONIDATION
ADE: Gray baby syndrome - newborns don’t have enz to metab. this= gray skin color
Chloramphenicol DIs and effects
Prolongs serum conc. of Phenytoin, Tolbutamide, Chlorpropramide, Warfarin
Like other bacteriostatic drugs, this antagonizes bactericidal drugs such as Pen/Aminoglycosides
AGs bind to 30S ribo in 3 ways
1) Interference w initiation complex
2) Misreading mRNA
3) Breakup of polysomes
AG ADEs
Nephrotoxicity- inc. serum creatinine and BUN (blood urea Nitrogen) levels
Neo, Tobra and Genta- most Nephx
Ototoxicity- auditory damage Neo, Kana, Amika
Vestibulotoxic- Strep, Genta
Mechanism. Binds to bacterial ribosome’s to inhibit protein synthesis.
Therapeutic use. Methicillin resistant S. aureus (MRSA) infections
Oxazolidinones: Linezolid (po, parenteral)
SE Reversible thrombocytopenia.
DI It can cause serotonin syndrome with antidepressants.
